The present disclosure methods and kits for use of stimulator of interferon genes (STING) agonist compounds, such as cyclic dinucleotides, amidobenzimidazoles, and benzothiophenes, in the treatment and prevention of pain, such as neuropathic pain, inflammatory pain, and cancer pain. Combination therapies and pharmaceutical formulations for treating of pain are also described.

The present disclosure methods and kits for use of stimulator of interferon genes (STING) agonist compounds, such as cyclic dinucleotides, amidobenzimidazoles, and benzothiophenes, in the treatment and prevention of pain, such as neuropathic pain, inflammatory pain, and cancer pain. Combination therapies and pharmaceutical formulations for treating of pain are also described.

The present invention provides a Pro-cyclic dinucleotide (Pro-CDN) comprising a STING agonist cyclic dinucleotide which is coupled to a linker system. The Pro-CDNs of the present invention can be metabolized at a targeted site into CDNs and exert their full immunomodulatory effects at said targeted site. The present invention also provides conjugates wherein a Pro-CDN is conjugated to a Biologically Active Molecule (BAM) such as e.g. a cytotoxic molecule, a lipid, a protein, a peptide, a nucleic acid, a sugar or a PRR ligand. The invention provides also methods related to the use of such compounds to perform their activities at their targeted sites, to exert cytotoxic, cytostatic or immunomodulatory effects, to treat or to prevent diseases such as cancers, immunological disorders or infections.

The present invention provides a Pro-cyclic dinucleotide (Pro-CDN) comprising a STING agonist cyclic dinucleotide which is coupled to a linker system. The Pro-CDNs of the present invention can be metabolized at a targeted site into CDNs and exert their full immunomodulatory effects at said targeted site. The present invention also provides conjugates wherein a Pro-CDN is conjugated to a Biologically Active Molecule (BAM) such as e.g. a cytotoxic molecule, a lipid, a protein, a peptide, a nucleic acid, a sugar or a PRR ligand. The invention provides also methods related to the use of such compounds to perform their activities at their targeted sites, to exert cytotoxic, cytostatic or immunomodulatory effects, to treat or to prevent diseases such as cancers, immunological disorders or infections.

A composition of matter comprising an α-ketoglutarate (AKG) or an α-ketoglutaric acid or a salt of an α-ketoglutarate may be used to treat patients having a neurodegenerative disease, such as amyotrophic lateralsclerosis. The composition may be administered hourly or may be administered once a day depending on the size and activity of the patient and the release coating or mechanism provided. In addition to AKG, a core composition may comprise GABA and a source of coenzyme Q10. Other substances may be provided either orally or intravenous in addition to the core composition, as required to control symptoms, or in order to stimulate stem cells to add motor neurons.

A composition of matter comprising an α-ketoglutarate (AKG) or an α-ketoglutaric acid or a salt of an α-ketoglutarate may be used to treat patients having a neurodegenerative disease, such as amyotrophic lateralsclerosis. The composition may be administered hourly or may be administered once a day depending on the size and activity of the patient and the release coating or mechanism provided. In addition to AKG, a core composition may comprise GABA and a source of coenzyme Q10. Other substances may be provided either orally or intravenous in addition to the core composition, as required to control symptoms, or in order to stimulate stem cells to add motor neurons.

Compositions comprising aldehyde functional monoterpenoids in combination with 3,3′,4′,7-tetrahydroxyflavone, zinc, and a 5-beta-D-Ribofuranosylpicolineamide adenine-dinucleotide molecule are provided for treating viral infections, e.g., coronavirus infections such as COVID-19, and/or enhancing mood.

Compositions comprising aldehyde functional monoterpenoids in combination with 3,3′,4′,7-tetrahydroxyflavone, zinc, and a 5-beta-D-Ribofuranosylpicolineamide adenine-dinucleotide molecule are provided for treating viral infections, e.g., coronavirus infections such as COVID-19, and/or enhancing mood.

Provided herein are methods of preparing EVs, e.g., exosomes, associated with or encapsulated various cyclic dinucleotides, including STING agonists. Also provided herein are methods of loading EVs, e.g., exosomes, with various cyclic dinucleotides, including STING agonists.

Provided herein are methods of preparing EVs, e.g., exosomes, associated with or encapsulated various cyclic dinucleotides, including STING agonists. Also provided herein are methods of loading EVs, e.g., exosomes, with various cyclic dinucleotides, including STING agonists.